The research proposed here will investigate neurobehavioral determinants of ethanol (ETOH) tolerance and the reinforcing effects of ETOH. Determination of the effects of chronic injection of ETOH on brain stimulation reward (BSR) at several brain sites of rats will be made. Three parameters of BSR will be measured simultaneously at each brain site: threshold of reward, rate of response and average brain impedance. A behavioral research design which permits determination of "learned" vs "unlearned" tolerance will be employed. Experiments are designed to 1. systematically investigate acute and chronic ETOH administration at specific brain loci, 2. determine learned and unlearned tolerance effects on BSR at each site, 3. investigate monoaminergic neuro-transmitter systems in learned and unlearned tolerance, and 4. examine the role of selected neurohormone systems in learned and unlearned tolerance. With time permitting, additional investigations of conditioning factors in both tolerance, other neuro-transmitters and neuropeptides, and other drugs which are "cross-tolerant" with ETOH will be investigated. The proposed studies are behavioral (psychological), pharmacological and biochemical. They should collectively shed important light on ETOH tolerance reinforcement produced by ETOH and brain sites which mediate these effects.